IL243117B2 - Oligosaccharides containing an amino group and their conjugates - Google Patents
Oligosaccharides containing an amino group and their conjugatesInfo
- Publication number
- IL243117B2 IL243117B2 IL243117A IL24311715A IL243117B2 IL 243117 B2 IL243117 B2 IL 243117B2 IL 243117 A IL243117 A IL 243117A IL 24311715 A IL24311715 A IL 24311715A IL 243117 B2 IL243117 B2 IL 243117B2
- Authority
- IL
- Israel
- Prior art keywords
- oligosaccharide
- group
- aminooxy
- reactive group
- chosen
- Prior art date
Links
- 229920001542 oligosaccharide Polymers 0.000 title claims description 167
- 150000002482 oligosaccharides Chemical class 0.000 title claims description 167
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 title claims description 50
- -1 aminooxy compound Chemical class 0.000 claims description 105
- 238000000034 method Methods 0.000 claims description 73
- 125000006239 protecting group Chemical group 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 21
- 230000008878 coupling Effects 0.000 claims description 17
- 238000010168 coupling process Methods 0.000 claims description 17
- 238000005859 coupling reaction Methods 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 16
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 6
- 150000001266 acyl halides Chemical class 0.000 claims description 5
- 150000008064 anhydrides Chemical class 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 239000012948 isocyanate Substances 0.000 claims description 5
- 150000002513 isocyanates Chemical class 0.000 claims description 5
- 150000002540 isothiocyanates Chemical class 0.000 claims description 5
- 150000001350 alkyl halides Chemical class 0.000 claims description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000002128 sulfonyl halide group Chemical group 0.000 claims description 2
- 235000018102 proteins Nutrition 0.000 description 39
- 108090000623 proteins and genes Proteins 0.000 description 39
- 102000004169 proteins and genes Human genes 0.000 description 39
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical group OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 26
- 108090000288 Glycoproteins Proteins 0.000 description 25
- 102000003886 Glycoproteins Human genes 0.000 description 25
- 102000004190 Enzymes Human genes 0.000 description 22
- 108090000790 Enzymes Proteins 0.000 description 22
- 208000015439 Lysosomal storage disease Diseases 0.000 description 20
- 230000002132 lysosomal effect Effects 0.000 description 18
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 8
- 102000004157 Hydrolases Human genes 0.000 description 8
- 108090000604 Hydrolases Proteins 0.000 description 8
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 201000004502 glycogen storage disease II Diseases 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 150000002772 monosaccharides Chemical class 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 208000024720 Fabry Disease Diseases 0.000 description 6
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 5
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 5
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- 230000005856 abnormality Effects 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000021615 conjugation Effects 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 238000000502 dialysis Methods 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 210000003712 lysosome Anatomy 0.000 description 5
- 230000001868 lysosomic effect Effects 0.000 description 5
- 125000003544 oxime group Chemical group 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 150000003384 small molecules Chemical class 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 229930105110 Cyclosporin A Natural products 0.000 description 4
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 4
- 108010036949 Cyclosporine Proteins 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 4
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 description 4
- 102000010126 acid sphingomyelin phosphodiesterase activity proteins Human genes 0.000 description 4
- 125000003368 amide group Chemical group 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 4
- 229960002170 azathioprine Drugs 0.000 description 4
- 125000003636 chemical group Chemical group 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 229960000485 methotrexate Drugs 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000010647 peptide synthesis reaction Methods 0.000 description 4
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- PZUPAGRIHCRVKN-UHFFFAOYSA-N 5-[5-[3,4-dihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]-5-[3,4,5-trihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]oxan-2-yl]oxyoxan-2-yl]oxy-3,4-dihydroxy-6-[(3,4,5-trihydroxyoxan-2-yl)oxymethyl]oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound OCC1OC(O)C(O)C(O)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(COC4C(C(O)C(O)CO4)O)O3)O)C(COC3C(C(O)C(O)CO3)O)O2)O)C(COC2C(C(O)C(O)CO2)O)O1 PZUPAGRIHCRVKN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 229920002527 Glycogen Polymers 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 150000001265 acyl fluorides Chemical class 0.000 description 3
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 150000002016 disaccharides Chemical class 0.000 description 3
- 229930182830 galactose Natural products 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 229940096919 glycogen Drugs 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000005629 sialic acid group Chemical group 0.000 description 3
- 210000001626 skin fibroblast Anatomy 0.000 description 3
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- 108060007951 sulfatase Proteins 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
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- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- 150000004044 tetrasaccharides Chemical class 0.000 description 3
- 231100001274 therapeutic index Toxicity 0.000 description 3
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- 150000004043 trisaccharides Chemical class 0.000 description 3
- 229910001868 water Inorganic materials 0.000 description 3
- UWROMLKEISLXAJ-UHFFFAOYSA-N (aminooxyamino)thiourea Chemical compound NONNC(N)=S UWROMLKEISLXAJ-UHFFFAOYSA-N 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- GMKMEZVLHJARHF-UHFFFAOYSA-N 2,6-diaminopimelic acid Chemical compound OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 2
- QBXODCKYUZNZCY-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]oxyacetic acid Chemical compound CC(C)(C)OC(=O)NOCC(O)=O QBXODCKYUZNZCY-UHFFFAOYSA-N 0.000 description 2
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 2
- JUQLUIFNNFIIKC-UHFFFAOYSA-N 2-aminopimelic acid Chemical compound OC(=O)C(N)CCCCC(O)=O JUQLUIFNNFIIKC-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- 102000009133 Arylsulfatases Human genes 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
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- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 description 2
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 2
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- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
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- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 2
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- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
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- PYLIXCKOHOHGKQ-UHFFFAOYSA-L disodium;hydrogen phosphate;heptahydrate Chemical compound O.O.O.O.O.O.O.[Na+].[Na+].OP([O-])([O-])=O PYLIXCKOHOHGKQ-UHFFFAOYSA-L 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
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- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 206010019847 hepatosplenomegaly Diseases 0.000 description 2
- ZTVZLYBCZNMWCF-UHFFFAOYSA-N homocystine Chemical compound [O-]C(=O)C([NH3+])CCSSCCC([NH3+])C([O-])=O ZTVZLYBCZNMWCF-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 230000001861 immunosuppressant effect Effects 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
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- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (2)
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| PCT/US2008/051429 WO2008089403A2 (en) | 2007-01-18 | 2008-01-18 | Oligosaccharides comprising an aminooxy group and conjugates thereof |
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| IL243117B IL243117B (en) | 2022-11-01 |
| IL243117B2 true IL243117B2 (en) | 2023-03-01 |
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| IL199925A IL199925A (en) | 2007-01-18 | 2009-07-16 | Oligosaccharides containing an aminoxic group and their bracelets |
| IL222792A IL222792A0 (en) | 2007-01-18 | 2012-11-01 | Method of coupling an oligosaccharide to a protein, oligosaccharide-protein conjugates, uses thereof and pharmaceutical compositions comprising the same |
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| IL222792A IL222792A0 (en) | 2007-01-18 | 2012-11-01 | Method of coupling an oligosaccharide to a protein, oligosaccharide-protein conjugates, uses thereof and pharmaceutical compositions comprising the same |
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| EP (5) | EP2457919B1 (pl) |
| JP (6) | JP5999867B2 (pl) |
| CN (2) | CN101631794B (pl) |
| CA (1) | CA2675968C (pl) |
| CY (2) | CY1119954T1 (pl) |
| DK (3) | DK2457919T3 (pl) |
| ES (3) | ES2744574T3 (pl) |
| FR (1) | FR22C1061I2 (pl) |
| HR (3) | HRP20130744T1 (pl) |
| HU (3) | HUE045046T2 (pl) |
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| PT (3) | PT2457920T (pl) |
| SI (2) | SI2457920T1 (pl) |
| WO (1) | WO2008089403A2 (pl) |
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